Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-gamma activation after stress in rats.
Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-gamma activation after stress in rats.
复制标题
应激介质在大鼠应激后调节大脑前列腺素合成和过氧化物酶体增殖物激活受体-γ激活。
作者：
B. García;J. Madrigal;B. Perez;J. Leza
应激暴露导致氧化/亚硝化和神经炎症变化，这些变化已被证明是由大脑中的神经递质通路调节的。特别是，急性束缚应激后，环氧合酶（考克斯）-2上调和随后的促炎性前列腺素（PG）E2释放在大鼠大脑皮层。同时，也产生了前列腺素15 d-PGJ（2）的合成及其核靶点过氧化物酶体增殖物激活受体（PPAR）-γ的激活。本研究旨在确定主要的应激介质：儿茶酚胺，糖皮质激素和兴奋性氨基酸（谷氨酸）在上述应激相关效应中的可能作用。通过使用特定的药理学工具，我们的研究结果表明，应激反应的主要介质涉及急性束缚应激暴露后大鼠脑皮质中前列腺素合成和PPARgamma激活的调节。中枢神经系统中应激释放的儿茶酚胺的药理学抑制（主要通过β-肾上腺素能受体）通过减少考克斯-2过表达和减少PPAR γ活化来调节15 d-PGJ（2）和PGE（2）的合成。应激产生的糖皮质激素通过与盐皮质激素和糖皮质激素受体的相互作用以非常相似的程度对前列腺素合成产生影响。然而，在PPARgamma调节的情况下，只有通过糖皮质激素受体的作用似乎是相关的。最后，在应激后选择性阻断N-甲基-d-天冬氨酸型谷氨酸受体也通过考克斯-2下调和减少PPARgamma转录活性和表达来负调节15 d-PGJ（2）和PGE（2）的产生。总之，我们在这里表明，主要的应激介质，儿茶酚胺，GC和谷氨酸，伴随着调节激活的促炎和炎症通路在一个可能的协同调节机制，急性束缚应激暴露诱导大鼠大脑皮层的炎症过程。
Stress exposure leads to oxidative/nitrosative and neuroinflammatory changes that have been shown to be regulated by antiinflammatory pathways in the brain. In particular, acute restraint stress is followed by cyclooxygenase (COX)-2 up-regulation and subsequent proinflammatory prostaglandin (PG) E2 release in rat brain cortex. Concomitantly, the synthesis of the antiinflammatory prostaglandin 15d-PGJ(2) and the activation of its nuclear target the peroxisome proliferator-activated receptor (PPAR)-gamma are also produced. This study aimed to determine the possible role of the main stress mediators: catecholamines, glucocorticoids, and excitatory amino acids (glutamate) in the above-mentioned stress-related effects. By using specific pharmacological tools, our results show that the main mediators of the stress response are implicated in the regulation of prostaglandin synthesis and PPARgamma activation in rat brain cortex described after acute restraint stress exposure. Pharmacological inhibition (predominantly through beta-adrenergic receptor) of the stress-released catecholamines in the central nervous system regulates 15d-PGJ(2) and PGE(2) synthesis, by reducing COX-2 overexpression, and reduces PPARgamma activation. Stress-produced glucocorticoids carry out their effects on prostaglandin synthesis through their interaction with mineralocorticoid and glucocorticoid receptors to a very similar degree. However, in the case of PPARgamma regulation, only the actions through the glucocorticoid receptor seem to be relevant. Finally, the selective blockade of the N-methyl-d-aspartate type of glutamate receptor after stress also negatively regulates 15d-PGJ(2) and PGE(2) production by COX-2 down-regulation and decrease in PPARgamma transcriptional activity and expression. In conclusion, we show here that the main stress mediators, catecholamines, GCs, and glutamate, concomitantly regulate the activation of proinflammatory and antiinflammatory pathways in a possible coregulatory mechanism of the inflammatory process induced in rat brain cortex by acute restraint stress exposure.
一氧化氮介导去甲肾上腺素诱导的下丘脑前列腺素 E2 释放。
DOI：
10.1073/pnas.89.23.11543
发表时间：
1992
影响因子：
11.1
作者：
Rettori,V;Gimeno,M;Lyson,K;McCann,SM
通讯作者：
McCann,SM
离体脑微血管以及正常和去甲肾上腺素刺激的猫脑匀浆中的前列腺素水平。
DOI：
10.1016/0090-6980(81)90156-8
发表时间：
1981
期刊：
Prostaglandins
影响因子：
--
作者：
Birkle,DL;Wright,KF;Ellis,CK;Ellis,EF
通讯作者：
Ellis,EF
影响因子：
15.9
作者：
VidalPuig, AJ;Considine, RV;Flier, JS
通讯作者：
Flier, JS